The Neisseria gonorrhoeae IpxLII gene encodes for a late-functioning lauroyl acyl transferase, and a null mutation within the gene has a significant effect on the induction of acute inflammatory responses

Ellis, CD Lindner, B Khan, CMA Zahringer, U de Hormaeche, RD

Cd. Ellis et al., The Neisseria gonorrhoeae IpxLII gene encodes for a late-functioning lauroyl acyl transferase, and a null mutation within the gene has a significant effect on the induction of acute inflammatory responses, MOL MICROB, 42(1), 2001, pp. 167-181

65

INGLESE

Article

Microbiology

MOLECULAR MICROBIOLOGY

0950-382X → ACNP

42

1

2001

167 - 181

ISI

0950-382X(200110)42:1<167:TNGIGE>2.0.ZU;2-0

LPS is a fundamental constituent of the outer membrane of all Gram-negative bacteria, and the lipid A domain plays a central role in the induction of inflammatory responses. We identified genes of the Neisseria gonorrhoeae li pid A biosynthetic pathway by searching the complete gonococcal genome sequ ence with sequences of known enzymes from other species. The IpxLII gene wa s disrupted by an insertion-deletion in an attenuated aroA mutant of the go nococcal strain MS11. Lipopolysaccharide (LPS) and lipid A analysis demonst rated that the IpxLII mutant had synthesized an altered LPS molecule lackin g a single lauric fatty acid residue in the GlcN II of the lipid A backbone . LPS of the IpxLII mutant had a markedly reduced ability to induce the pro inflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL) -1 beta, IL-6 and IL-8 from human macrophages and IL-8 from polymorphonucle ar cells. This study demonstrates that the IpxLII gene in gonococci encodes for a late-functioning lauroyl acyl transferase that adds a lauric acid at position 2' in the lipid A backbone. The presence of lauric acid at such a position appears to be crucial for the induction of full inflammatory resp onses by N. gonorrhoeae LPS.